On 12 Apr 2002 at 14:17:33, David Jaworowicz (david.jaworowicz.-at-.cognigencorp.com) sent the message

Dear T. Hoppe-Tichy

This equation is an alternative to more formal calculations of theaccumulation factor R.

R can be calculated as the ratio of drug concentrations observed during adosing interval at steady-state divided by drug concentrations seen duringthe dosing interval after a single (first) dose, as described by thefollowing equations:

R= steady state AUC(0-tau) / single dose AUC(0-tau) where tau is dosinginterval.

Also, calculated by: R=Cmin(steady-state) / Cmin(single-dose)

Note: steady state AUC(0-tau) is equal to AUC(0-infinity) after a singledose.If your dosing interval is long enough such that all drug is eliminatedbefore a subsequent dose, the resulting R value = 1, since both the numeratorand denominator should be equal, and obviously no accumulation will occur.The equation R=1/(1-e^-Kel t) presented in your e-mail, represents asimplified way of calculating R without the need to obtain steady-statedata. As can be seen in this equation, R is a function of tau and theterminal elimination rate constant (and is independent of dose). Longer keland shorter tau will result in R>1. Technically, R should never go below 1(unless someone knows of situations of metabolic induction, etc. that mayproduce artifactual results?).

On 28 May 2002 at 12:44:16, (icrgregoire.-a-.yahoo.com) sent the message

Dear all,

I would appreciate if any members of PharmPK can advise me on how tocalculate (and interpret) theoretical accumulation ratio (AR) whenusing a two-compartment model.

Thank you;

Nicolas GREGOIRE.

[Moderator note - I have received a few messages recently that startwith 'PharmPK' in the subject line. The problem is that I have thelistserv software set up to add this to the subject on the way out.Thus, messages with PharmPK in the beginning of the message look tome like messages that have already been sent out and I may 'ignore'them. Thus, the best approach is to send the message toPharmPK.-a-.boomer.org with a descriptive subject without using PharmPK.Replying to a message with a comment on the same topic usually workswell as a Re: (or similar) is usually added and this cues me torecognize a new message Thanks - db]